-
Scientific Reports Jun 2024This study investigates quercetin complexes as potential synergistic agents against the important respiratory pathogen Streptococcus pneumoniae. Six quercetin complexes...
This study investigates quercetin complexes as potential synergistic agents against the important respiratory pathogen Streptococcus pneumoniae. Six quercetin complexes (QCX1-6) were synthesized by reacting quercetin with various metal salts and boronic acids and characterized using FTIR spectroscopy. Their antibacterial activity alone and in synergism with antibiotics was evaluated against S. pneumoniae ATCC 49619 using disc diffusion screening, broth microdilution MIC determination, and checkerboard assays. Complexes QCX-3 and QCX-4 demonstrated synergy when combined with levofloxacin via fractional inhibitory concentration indices ≤ 0.5 as confirmed by time-kill kinetics. Molecular docking elucidated interactions of these combinations with virulence enzymes sortase A and sialidase. A biofilm inhibition assay found the synergistic combinations more potently reduced biofilm formation versus monotherapy. Additionally, gene-gene interaction networks, biological activity predictions and in-silico toxicity profiling provided insights into potential mechanisms of action and safety.
Topics: Streptococcus pneumoniae; Quercetin; Anti-Bacterial Agents; Biofilms; Molecular Docking Simulation; Microbial Sensitivity Tests; Drug Synergism; Bacterial Proteins; Cysteine Endopeptidases; Aminoacyltransferases; Neuraminidase
PubMed: 38834612
DOI: 10.1038/s41598-024-62782-w -
MBio Jun 2024A crucial step in lowering the risk of invasive pneumococcal illness in high-risk populations, such as individuals with plaque psoriasis, is pneumococcal vaccination....
UNLABELLED
A crucial step in lowering the risk of invasive pneumococcal illness in high-risk populations, such as individuals with plaque psoriasis, is pneumococcal vaccination. The serologic response to the sequential vaccination with Prevenar 13 (PCV13) and Pneumovax 23 (PPSV23) in psoriasis patients under immunosuppressive therapy is still poorly characterized despite national recommendations suggesting vaccination for immunocompromised patients. In this prospective study, we investigated the serological response in 57 patients under active systemic treatment for moderate to severe plaque psoriasis who underwent sequential vaccination with PCV13 followed by PPSV23. Our analysis focused on global and serotype-specific anti-pneumococcal antibody responses over a 7-month period post-vaccination. Our findings reveal a robust serological response in patients with plaque psoriasis under systemic therapy. When comparing our results with a cohort of kidney transplant recipients who completed a similar sequential vaccination protocol, psoriasis patients showed higher antibody concentrations. In psoriasis patients, the mean levels of all global antibody classes tested (IgG, IgG2, IgA, IgM) increased more than 4-fold ( < 0.0001) and serotype-specific antibodies more than 1.9-fold ( < 0.01). In addition to providing strong evidence of the safety and effectiveness of sequential pneumococcal vaccination in individuals with plaque psoriasis, our work sheds light on the complex interactions that exist between immunosuppressive treatment, vaccination schedule, and antibody responses in various risk groups.
IMPORTANCE
To protect against severe courses of infection with , the national guidelines recommend sequential vaccination for these patients. However, there are only studies on the efficacy of a single administration of these vaccines in this particular risk group. The immunological responses to the vaccine were correlated with clinical patient data. In summary, our study shows for the first time that sequential vaccination is immunogenic in patients with moderate to severe plaque psoriasis.
PubMed: 38832785
DOI: 10.1128/mbio.00482-24 -
Infection Jun 2024To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic.
PURPOSE
To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic.
METHODS
In a Dutch prospective cohort, risk factors and clinical characteristics of pneumococcal meningitis episodes occurring during the COVID-19 pandemic (starting March 2020) were compared with those from baseline and the time afterwards. Outcomes were compared with an age-adjusted logistic regression model.
RESULTS
We included 1,699 patients in 2006-2020, 50 patients in 2020-2021, and 182 patients in 2021-2023. After March 2020 relatively more alcoholism was reported (2006-2020, 6.1%; 2020-2021, 18%; 2021-2023, 9.7%; P = 0.002) and otitis-sinusitis was less frequently reported (2006-2020, 45%; 2020-2021, 22%; 2021-2023, 47%; P = 0.006). Other parameters, i.e. age, sex, symptom duration or initial C-reactive protein level, remained unaffected. Compared to baseline, lumbar punctures were more frequently delayed (on admission day, 2006-2020, 89%; 2020-2021, 74%; 2021-2022, 86%; P = 0.002) and outcomes were worse ('good recovery', 2020-2021, OR 0.5, 95% CI 0.3-0.8).
CONCLUSION
During the COVID-19 pandemic, we observed worse outcomes in patients with pneumococcal meningitis. This may be explained by differing adherence to restrictions according to risk groups or by reduced health care quality.
PubMed: 38831205
DOI: 10.1007/s15010-024-02305-x -
PeerJ 2024The use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World...
BACKGROUND
The use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria.
OBJECTIVES
This aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a model of infection.
METHODS
A chronic model of infection in larvae was used for the experiment. Inoculation of larvae with was followed by injections of erythromycin ADI doses (0.0875 and 0.012 μg/ml according to EMA and WHO, respectively). Isolation of colonies was then performed on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications.
RESULTS
Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in . Emergent resistance to erythromycin was associated with a mutation in , which codes for the L1 ribosomal protein and has been linked to macrolide resistance in previous studies.
CONCLUSION
In our model, even single doses of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in . These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs.
Topics: Erythromycin; Animals; Streptococcus pneumoniae; Microbial Sensitivity Tests; Anti-Bacterial Agents; Moths; Drug Resistance, Bacterial; Larva; Pneumococcal Infections; Disease Models, Animal; Humans
PubMed: 38827315
DOI: 10.7717/peerj.17463 -
Marine Life Science & Technology May 2024Bacteria with functional DNA repair systems are expected to have low mutation rates due to strong natural selection for genomic stability. However, our study of the...
UNLABELLED
Bacteria with functional DNA repair systems are expected to have low mutation rates due to strong natural selection for genomic stability. However, our study of the wild-type D39, a pathogen responsible for many common diseases, revealed a high spontaneous mutation rate of 0.02 per genome per cell division in mutation-accumulation (MA) lines. This rate is orders of magnitude higher than that of other non-mutator bacteria and is characterized by a high mutation bias in the A/T direction. The high mutation rate may have resulted from a reduction in the overall efficiency of selection, conferred by the tiny effective population size in nature. In line with this, D39 also exhibited the lowest DNA mismatch-repair (MMR) efficiency among bacteria. Treatment with the antibiotic penicillin did not elevate the mutation rate, as penicillin did not induce DNA damage and lacks a stress response pathway. Our findings suggested that the MA results are applicable to within-host scenarios and provide insights into pathogen evolution.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42995-024-00220-6.
PubMed: 38827133
DOI: 10.1007/s42995-024-00220-6 -
International Journal of Medical... Jun 2024We report a case of bacteremia with pyelonephritis in an adult male with an underlying disease caused by α-hemolytic streptococci. α-Hemolytic streptococci were...
OBJECTIVES
We report a case of bacteremia with pyelonephritis in an adult male with an underlying disease caused by α-hemolytic streptococci. α-Hemolytic streptococci were isolated from blood, but it was challenging to identify its species. This study aimed to characterize the causative bacterium SP4011 and to elucidate its species.
METHODS
The whole-genome sequence and biochemical characteristics of SP4011 were determined. Based on the genome sequence, phylogenetic analysis was performed with standard strains of each species of α-hemolytic streptococci. Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values were calculated.
RESULTS
SP4011 showed optochin susceptibility and bile solubility, but did not react with pneumococcal omni antiserum. Phylogenetic analysis of the whole-genome sequence showed that SP4011 clustered with S. pneumoniae and S. pseodopneumoniae and was most closely related to S. pseodopneumoniae. Genomic analysis revealed that ANI and dDDH values between SP4011 and S. pseodopneumoniae were 94.0 % and 56.0 %, respectively, and between SP4011 and S. pneumoniae were 93.3 % and 52.2 %, respectively. Biochemical characteristics also showed differences between SP4011 and S. pseodopneumoniae and between SP4011 and S. pneumoniae. These results indicate that SP4011 is a novel species.
CONCLUSION
Our findings indicate that SP4011 is a novel species of the genus Streptococcus. SP4011 has biochemical characteristics similar to S. pneumoniae, making it challenging to differentiate and requiring careful clinical diagnosis. This isolate was proposed to be a novel species, Streptococcus parapneumoniae sp. nov. The strain type is SP4011 (= JCM 36068 = KCTC 21228).
Topics: Humans; Male; Streptococcal Infections; Phylogeny; Bacteremia; Streptococcus; Pyelonephritis; Genome, Bacterial; DNA, Bacterial; Whole Genome Sequencing; Anti-Bacterial Agents; Nucleic Acid Hybridization; Bacterial Typing Techniques; Microbial Sensitivity Tests; Middle Aged
PubMed: 38824713
DOI: 10.1016/j.ijmm.2024.151625 -
PloS One 2024Urinary tract infections are common bacterial and fungal infections in humans, occurring both in the community and in immunocompromised patients in healthcare settings....
Uro-pathogens: Multidrug resistance and associated factors of community-acquired UTI among HIV patients attending antiretroviral therapy in Dessie Comprehensive Specialized Hospital, Northeast Ethiopia.
BACKGROUND
Urinary tract infections are common bacterial and fungal infections in humans, occurring both in the community and in immunocompromised patients in healthcare settings. Urinary tract infections have a significant health impact on HIV-infected patients. Nowadays, drug-resistant pathogens are widespread poses a serious clinical risk, and causes urinary tract infection. The common agents of bacteria and fungi that cause urinary tract infection are Escherichia coli followed by Klebsiella pneumonia, Staphylococcus saprophyticus, Enterococcus faecalis, group B streptococcus, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida. albicans. This study aimed to investigate uro-pathogen, multidrug resistance pattern of bacteria, and associated factors of community-acquired urinary tract infection among HIV-positive patients attending antiretroviral therapy in Dessie comprehensive specialized hospital, Northeast Ethiopia from February 1, 2021, to March 30, 2021.
METHODS
An institutional-based cross-sectional study was conducted at Dessie Comprehensive Specialized Hospital. Socio-demographic and clinical data were collected by using structured questionnaires from HIV patients suspected of community-acquired urinary tract infections. About 10 ml of clean-catch midstream urine was collected and inoculated into Blood agar, MacConkey, and Cysteine lactose electrolyte deficient media. Yeasts were identified by using Gram stain, germ tube test, carbohydrate fermentation, assimilation tests, and chromogenic medium. Gram stain and biochemical tests were performed to identify isolates and an antimicrobial susceptibility pattern was performed on disc diffusion techniques. Data were entered and analyzed using SPSS version 25. Both bivariate and multivariable logistic regression analysis was performed and a P value of < 0.05 with an adjusted odds ratio with their 95% confidence interval (CI) was used as statistically significant associations.
RESULTS
From the total 346 study participants, 92 (26.6%) were culture positive 75 (81.52%) were bacterial and 17 (18.48%) were fungal pathogens. From a total of 75 bacteria isolates 51(68%) were Gram-negative bacteria and the most commonly isolated bacteria were E. coli 16 (21.33%) followed by K. pneumoniae 11(14.67%) and enterococcus species 10(10.87. Of the 17 fungal isolates of fungi, 8(47.1%) were represented by C. tropicalis. Of the isolated bacteria, 61(81.3%) were resistant to three and above classes of antibiotics (drug classes). About 13 (81.3%) of E. coli, 9(81.8%) of K. pneumoniae, 8(80%) of Enterococcus species, 7 (77.8%) of P. aeruginosa, and CoNs 7(87.5%) were the most frequently exhibited three and above classes of antibiotics (multi-drug resistance). Amikacin and gentamicin were effective against Gram-negative Uro-pathogens. Participants aged>44year, female, being daily labor, being farmer, unable to read and write, patients with CD4 count of ≤ 200 cells/mm3 and CD4 count of 201-350 cells/mm3, who had chronic diabetics, patients having a history of hospitalization and who had urgency of urinations were statistically significant association with significant urinary tract infections.
CONCLUSION
The burden of community-acquired urinary tract infections among HIV patients is alarmingly increased. Therefore, behavior change communications might be considered for promoting the health status of HIV patients. Moreover, CD4 level monitoring and therapeutics selection based on microbiological culture are quite advisable for the management of urinary tract infections of HIV patients.
Topics: Humans; Ethiopia; Urinary Tract Infections; Female; Male; HIV Infections; Adult; Community-Acquired Infections; Middle Aged; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Young Adult; Microbial Sensitivity Tests; Anti-Bacterial Agents; Hospitals, Special; Bacteria
PubMed: 38820330
DOI: 10.1371/journal.pone.0296480 -
Scientific Reports May 2024Klebsiella pneumoniae releases the peptides AKTIKITQTR and FNEMQPIVDRQ, which bind the pneumococcal proteins AmiA and AliA respectively, two substrate-binding proteins...
Klebsiella pneumoniae releases the peptides AKTIKITQTR and FNEMQPIVDRQ, which bind the pneumococcal proteins AmiA and AliA respectively, two substrate-binding proteins of the ABC transporter Ami-AliA/AliB oligopeptide permease. Exposure to these peptides alters pneumococcal phenotypes such as growth. Using a mutant in which a permease domain of the transporter was disrupted, by growth analysis and epifluorescence microscopy, we confirmed peptide uptake via the Ami permease and intracellular location in the pneumococcus. By RNA-sequencing we found that the peptides modulated expression of genes involved in metabolism, as pathways affected were mostly associated with energy or synthesis and transport of amino acids. Both peptides downregulated expression of genes involved in branched-chain amino acid metabolism and the Ami permease; and upregulated fatty acid biosynthesis genes but differed in their regulation of genes involved in purine and pyrimidine biosynthesis. The transcriptomic changes are consistent with growth suppression by peptide treatment. The peptides inhibited growth of pneumococcal isolates of serotypes 3, 8, 9N, 12F and 19A, currently prevalent in Switzerland, and caused no detectable toxic effect to primary human airway epithelial cells. We conclude that pneumococci take up K. pneumoniae peptides from the environment via binding and transport through the Ami permease. This changes gene expression resulting in altered phenotypes, particularly reduced growth.
Topics: Klebsiella pneumoniae; Bacterial Proteins; Streptococcus pneumoniae; Transcriptome; Gene Expression Regulation, Bacterial; Humans; Ligands; Membrane Transport Proteins; Peptides
PubMed: 38816440
DOI: 10.1038/s41598-024-63217-2 -
Research and Practice in Thrombosis and... May 2024Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5...
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5 (C5) inhibitors have decreased PNH-related thrombosis rates and reduced mortality compared with those of age-matched controls. A small but significantly increased risk of life-threatening infections, especially , represents a long-term safety risk of complement inhibition.
OBJECTIVES
To evaluate the rates of thrombosis and meningococcal infections in patients with PNH treated with the complement component 3-targeted therapy pegcetacoplan.
METHODS
Cumulative patient-year exposure to pegcetacoplan was calculated, and thrombotic events and meningococcal infections were reviewed in 7 clinical trials and in the postmarketing setting. The clinical trial protocols and pegcetacoplan labeling required vaccination against , , and before pegcetacoplan use; the label allowed for prophylactic antibiotic use if pegcetacoplan must be administered before vaccination.
RESULTS
As of November 13, 2022, 464 patients with PNH had 619.4 patient-years of pegcetacoplan exposure in completed/ongoing clinical trials and the postmarketing setting. Seven thrombotic events were reported: 5 in clinical trials (2 in the same patient) and 2 in the postmarketing setting. The overall thrombosis rate was 1.13 events per 100 patient-years (clinical trials: 1.22 events/100 patient-years in 409.4 years; postmarketing: 0.95 events/100 patient-years in 210.0 years). No infections with meningococcal bacteria were reported.
CONCLUSION
Event rates for thrombosis were comparable between pegcetacoplan and previously reported rates of C5 inhibitors in patients with PNH, and no cases of meningococcal infection were reported with pegcetacoplan. Continued follow-up is required.
PubMed: 38812989
DOI: 10.1016/j.rpth.2024.102416 -
Journal of Bacteriology Jun 2024The major human pathogen has been the subject of intensive clinical and basic scientific study for over 140 years. In multiple instances, these efforts have resulted in... (Review)
Review
The major human pathogen has been the subject of intensive clinical and basic scientific study for over 140 years. In multiple instances, these efforts have resulted in major breakthroughs in our understanding of basic biological principles as well as fundamental tenets of bacterial pathogenesis, immunology, vaccinology, and genetics. Discoveries made with have led to multiple major public health victories that have saved the lives of millions. Studies on continue today, where this bacterium is being used to dissect the impact of the host on disease processes, as a powerful cell biology model, and to better understand the consequence of human actions on commensal bacteria at the population level. Herein we review the major findings, i.e., puzzle pieces, made with and how, over the years, they have come together to shape our understanding of this bacterium's biology and the practice of medicine and modern molecular biology.
Topics: Animals; Humans; Bacteriology; History, 19th Century; History, 20th Century; History, 21st Century; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 38809015
DOI: 10.1128/jb.00059-24